To understand high quality trial/s on the topic of neurosurgery, specifically in intracerebral haemorrhage.

1.      Introduction: Purpose of review: to understand high quality trial/s on the topic of neurosurgery, specifically in intracerebral haemorrhage.

2.      Who wrote the paper: Hanley et al. conducted a randomised, controlled, open-label, blinded endpoint phase 3 trial, "Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III)," published in The Lancet (impact factor 98.4, Clarivate 2024). This global study involved 78 hospitals across the USA, Canada, Europe, Australia, and Asia, targeting healthcare professionals, researchers, and policymakers in neurology, neurosurgery, and stroke care.

3.      The hypothesis (PICO framework): The research question addressed the efficacy of [I: minimally invasive catheter evacuation followed by thrombolysis (MISTIE) in reducing clot size and improving functional outcomes], in [P: patients aged 18+ with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more], compared to [C: standard medical care]. [O: primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-3 at 365 days].

4.      Appraise the evidence base: Despite limited high-quality evidence from recent meta-analyses suggesting non-craniotomy surgical techniques might improve outcomes (citation), this study provides robust randomised controlled trial data to evaluate MISTIE's efficacy and safety, potentially influencing future guidelines and clinical practices (citation).

5.      Study design: a phase 3 RCT compared the efficacy and safety of MISTIE versus standard medical care in acute stroke patients aged 18 and older with non-traumatic, supratentorial intracerebral haemorrhage of at least 30 mL, focusing on severely affected individuals based on specific GCS and NIHSS scores. Exclusion criteria may affect generalizability. Participants were assigned using a computer-generated number sequence, with block randomization and covariate-adaptive randomization to reduce bias and minimize baseline differences.

6.      Are the methods thorough: The study employed systematic follow-up, using the modified Rankin Scale and NIHSS to assess functional outcomes. A modified intention-to-treat population was used for statistical analysis, with a power analysis targeting 88% power at an α level of 0.05 to detect a 13% effect size.

7.      Results: The primary efficacy outcome did not achieve the pre-specified significance level (P < 0.05), but some secondary analyses yielded statistically significant results, such as the odds ratios for different mRS scores (P = 0.03 for scores > 5).

8.      Discussion and interpretation: The multicentre, randomized, controlled trial with blinded endpoint assessment enhances generalizability and reduces bias, but the open-label design may introduce bias. The primary outcome did not reach statistical significance, questioning efficacy. The study provides insights into the safety and potential mortality reduction of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation but does not definitively support improved functional outcomes. Comparisons with the STICH trials and current guidelines are discussed.

9.      Clinical context: MISTIE III explores minimally invasive alternatives to traditional open craniotomy, emphasizing the importance of reducing clot size to ≤15 mL and potentially refining patient selection criteria for surgical interventions.

10.   Output (points to consider for a potential Letter to the editor): I) Patient selection criteria, especially intracerebral haemorrhage volume threshold and its influence on outcomes, require elucidation. II) Safety analysis should encompass rebleeding and infection rates post minimally invasive surgery with thrombolysis. III) Alteplase dosage selection and frequency rationale for optimal efficacy need explanation. IV) Long-term patient follow-up insights, assessing functional outcome sustainability beyond one year, are essential.